Comminution Processes in Drug Preparation

COMMINUTION Comminution is a general term for various processes used to reduce the particle size of drug materials. Comminution Processes: Cutting/Slicing is done with the aid of a sharp knife, shears or a root cutter. In the 19th century, machines were developed for large-scale work. Crushing/Contusion (or bruising or pounding) is the process of reducing a drug to small particles by striking it with several blows. From ancient times this was normally carried out in a mortar and pestle made of stone, wood, metal or, from the late 18 th century of ceramic composition. An alternative is a simple grater of the type still used in the kitchen for nutmeg or cheese. Grinding reduced a substance to a fine powder. This was normally achieved in a mor tar and pestle by using a revolving, shearing action rather than striking. Sieving is used to ensure that drugs had been sufficiently ground to produce a suitable particle size. Any oversized particles are removed from the ground drug. Vibrating: Trituration, for instance, is comminution (or substance breakdown) by rubbing. Trituration can further be described as levigation, trituration of a powder with an insoluble liquid, or pulverization by intervention, which is trituration with a solvent that can be easily removed after the substance, has been broken down. Importance of comminution: Comminution is very important in the preparation of pharmaceutical dispersions, paste and fluids where properties such as consistency, tendency to settle/sediment, appearance and the general storage characteristics, etc. all depend on the particle size of the solid ingredients. Comminution is also applied to a greater or lesser extent to most drugs in order to present a large surface area to the action of solvents, thus aiding dissolution of drugs and chemical substances. In the case of crude drugs, size reduction allows the rapid penetration of solvents into the material to extract their active constituents. Comminution is important in the preliminary stages in the preparation of compressed tablets where granular material (granulation) is required for the tabletting process. The particle size characteristics of the tablet excipients, such as; disintegrants, lubricants, diluents, etc, have a major influence on the properties of the finished tablets. Comminution is also required to reduced the materials to a very fine state of sub division in the preparation of products such as insufflations and ointments as well as suppositories and pessaries, where the solid constituents must be impalpable (< 60um in diameter) in order to avoid unwanted side effects, grittiness etc, and enhance bioavailability. Also, for sustained release formulations, the drug particles must be within a particular size range, if its effects are to be prolonged over a period as required, and avoid being excreted too rapidly from the body. Comminution Machinery: Machinery for size reduction may be divided into three broad classes, depending on the size product required or produced. These are; Coarse crushers: these usually accomplish breaking by the application of a continuous pressure. They yield products generally greater than 1000um in diameter. Intermediate machines: these employ blow and/or impact methods to achieve breaking or size reduction and produce powders in which the majority of particles are between 100-1000um in diameter. Fine (particle) machines: these employ grinding and or abrasion methods and are used to prepare the finest powders of about 1um in diameter or below. There is however, no sharp dividing line between these three classes of machines, but the intermediate and fine ones are of much interest than crushers. Mechanism of Comminution (size reduction) The mechanisms involved in size reduction are very complex and vary with the nature of the material. Many attempts have been made to develop a relationship for the useful work required to effect a given size reduction. However, theories of this nature are limited in use in the choice and operation of a Comminution machine. Art and experience are prime requirements in order to produce the desired result, since some drugs require individual treatment. Factors that affect/influence comminution [THEM] Toughness of the material and its crack propagation Hardness/surface hardness Moisture content (i.e. dry and wet grinding) Energy requirement of the process Examples of comminution machinery [HIPBiM] About five main types of equipment are in regular use for comminution/size reduction of drugs and other pharmaceutical materials. These are; Hand operated or mechanical pestles and mortars Impact or hammer mills Pin mills Ball mills and vibration mills Micronizers In addition to these, the techniques of spray drying and freeze drying, as well as crystallization and precipitation are being used to produce drugs in a fine state of subdivision without grinding/milling. (1) Mortar and pestle types E.g. (a) Hand mortar and pestle - small scale/laboratory use (b) Mechanical counterparts e.g. End runner mill Grinding action involves both impact and shear, thus, causing crushing and rubbing. Edge runner mill – Particle size reduction is by crushing and friction. It is used for tough and fibrous materials such as roots and barks, which are reduced to powder. (2) Impact or hammer mills e.g. The Apex Mill & Fritz Mill These are suitable for producing coarse to ultra fine powders (of >1um in diameter) from a varied groups of materials such as; drugs roots herbs glands, livers, soaps, etc. (3) Pin Mills e.g. Reddrop-Periflo Mill These are adapted for the fine grinding of substances with low melting points such as resin, soap, and sugars, etc. (4) Ball Mills e.g. Hardinge Mill The materials are ground by the impact and friction of a large number of balls in a rotating vessel. These produce fine powders, the fineness depending on the speed of the mill, the size, nature, path and load of the balls, and the charge of the material being handled. (5) Vibration Mills These are similar to the Ball Mill, but here the energy is supplied by vibrating the mill body. (6) Micronizing or jet milling This involves grinding particles upon themselves by circulating at high speed by air or superheated steam at high pressure. Mortar and pestle types Impact or hammer mills Pin Mills Ball Mill Vibration Mill Micronizers EFFICIENCY OF WET AND DRY GRINDING Grinding may be accomplished wet or dry. Wet grinding is normally done at 60% 80% solids by weight. The fluid is usually water. In dry grinding the moisture content is generally kept below 5%. Many materials can be ground wet or dry. The selection of wet or dry grinding depends on the moisture content of the feed material and on the moisture considerations for the discharged product or its further processing. If subsequent processing requires a dry material, then dry grinding is more efficient than wet grinding in that it requires less power per ton. Wet grinding tends to be preferred over dry grinding where other considerations leave essentially a free choice. Wet grinding is a milling process used to produce powder or paste from a solid using a liquid such as water. It can also be used in an abrasive process to reform hard objects. There are numerous items that can be processed in this way, including grains and ores. Such techniques are used for both domestic and industrial tasks. When used in industrial settings, a wet technique is often more economical than dry grinding. Wet grinding (i.e. the milling of materials in water or other liquid) is a process that has been around for a long time. The process was once executed using the mechanical energy of stones. Today, there are machines available that make the work much easier. Electric powered wet grinders come in many sizes. Some are small enough for countertop use in a domestic kitchen. Others are big enough for commercial use in industrial facilities. These machines usually involve wheels or balls used to mill materials as the liquid is fed into the mixture. This often results in a type of slushy mixture. Depending on the end use of the materials, they may have to be dried before they can be used. Electric grinders are often used in kitchens to reduce foods for the sake of consistency when making sauces or gravies. Many people use wet grinding to produce pastes and other items which are popular ingredients in their dishes. Wet grinding is often preferred by those in industrial settings because the process can have several advantages. It is less power intensive than dry grinding. This means more material can be ground using significantly less energy. Wet grinding also provides an economical means to produce fine granules. Dry grinding (i.e. reducing particle sizes without a liquid medium) is usually not comparable. Trying to produce fine particle sizes using a dry grinding technique can be very energy intensive and therefore expensive. Even when this is done, the particles still may not be as small as they would be if a wet process was used. When dry grinding is performed, there are often large amounts of dust created. This often requires investing in special equipment to capture or control that dust. With wet grinding, this type of investment is not usually necessary. The liquid involved in the wet grinding process can also make it a better choice. When items such as metal are ground, especially using a dry method, a great deal of heat can be generated. If there is a liquid present, such as with wet grinding, it can act as a coolant that can protect the worker, the machine, and the material being processed. Grinding may occur in an open or closed circuit. In open circuit grinding, material makes only one pass through the mill and is conveyed to storage or subsequent processing. In closed circuit grinding each pass through the mill is followed by classification. The coarse material is returned to the mill for additional grinding while the fine material is conveyed to storage or subsequent processing.